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- PDB-4p9h: Crystal structure of 8ANC195 Fab in complex with gp120 of 93TH057... -
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Open data
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Basic information
Entry | Database: PDB / ID: 4p9h | |||||||||||||||
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Title | Crystal structure of 8ANC195 Fab in complex with gp120 of 93TH057 HIV-1 and soluble CD4 D1D2 | |||||||||||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / IG FOLD / ANTI HIV / ANTIBODY / IMMUNE SYSTEM COMPLEX / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | ![]() helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation ...helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation / Alpha-defensins / positive regulation of kinase activity / regulation of T cell activation / T cell receptor complex / extracellular matrix structural constituent / Other interleukin signaling / enzyme-linked receptor protein signaling pathway / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / regulation of calcium ion transport / macrophage differentiation / Generation of second messenger molecules / T cell differentiation / PD-1 signaling / positive regulation of protein kinase activity / Binding and entry of HIV virion / coreceptor activity / positive regulation of calcium-mediated signaling / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of establishment of T cell polarity / positive regulation of interleukin-2 production / T cell activation / protein tyrosine kinase binding / host cell endosome membrane / Vpu mediated degradation of CD4 / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / transmembrane signaling receptor activity / positive regulation of peptidyl-tyrosine phosphorylation / Cargo recognition for clathrin-mediated endocytosis / Downstream TCR signaling / positive regulation of T cell activation / MHC class II protein complex binding / Clathrin-mediated endocytosis / virus receptor activity / signaling receptor activity / clathrin-dependent endocytosis of virus by host cell / positive regulation of canonical NF-kappaB signal transduction / defense response to Gram-negative bacterium / adaptive immune response / positive regulation of MAPK cascade / positive regulation of viral entry into host cell / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / early endosome / viral protein processing / cell adhesion / positive regulation of protein phosphorylation / immune response / membrane raft / endoplasmic reticulum lumen / fusion of virus membrane with host plasma membrane / external side of plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / lipid binding / virion attachment to host cell / endoplasmic reticulum membrane / protein kinase binding / host cell plasma membrane / virion membrane / structural molecule activity / positive regulation of DNA-templated transcription / enzyme binding / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||
Method | ![]() ![]() ![]() ![]() | |||||||||||||||
![]() | Scharf, L. / Bjorkman, P.J. | |||||||||||||||
![]() | ![]() Title: Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Authors: Louise Scharf / Johannes F Scheid / Jeong Hyun Lee / Anthony P West / Courtney Chen / Han Gao / Priyanthi N P Gnanapragasam / René Mares / Michael S Seaman / Andrew B Ward / Michel C ...Authors: Louise Scharf / Johannes F Scheid / Jeong Hyun Lee / Anthony P West / Courtney Chen / Han Gao / Priyanthi N P Gnanapragasam / René Mares / Michael S Seaman / Andrew B Ward / Michel C Nussenzweig / Pamela J Bjorkman / ![]() Abstract: Broadly neutralizing antibodies (bNAbs) to HIV-1 envelope glycoprotein (Env) can prevent infection in animal models. Characterized bNAb targets, although key to vaccine and therapeutic strategies, ...Broadly neutralizing antibodies (bNAbs) to HIV-1 envelope glycoprotein (Env) can prevent infection in animal models. Characterized bNAb targets, although key to vaccine and therapeutic strategies, are currently limited. We defined a new site of vulnerability by solving structures of bNAb 8ANC195 complexed with monomeric gp120 by X-ray crystallography and trimeric Env by electron microscopy. The site includes portions of gp41 and N-linked glycans adjacent to the CD4-binding site on gp120, making 8ANC195 the first donor-derived anti-HIV-1 bNAb with an epitope spanning both Env subunits. Rather than penetrating the glycan shield by using a single variable-region CDR loop, 8ANC195 inserted its entire heavy-chain variable domain into a gap to form a large interface with gp120 glycans and regions of the gp120 inner domain not contacted by other bNAbs. By isolating additional 8ANC195 clonal variants, we identified a more potent variant, which may be valuable for therapeutic approaches using bNAb combinations with nonoverlapping epitopes. | |||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 208 KB | Display | ![]() |
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PDB format | ![]() | 159.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.3 MB | Display | ![]() |
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Full document | ![]() | 2.3 MB | Display | |
Data in XML | ![]() | 37.6 KB | Display | |
Data in CIF | ![]() | 50.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 2625C ![]() 4p9mSC ![]() 3lqaS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Details | biological unit is the same as asym. |
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Components
-Protein , 2 types, 2 molecules CG
#1: Protein | Mass: 21444.273 Da / Num. of mol.: 1 / Fragment: CD4 D1D2 / Mutation: K75T Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 40274.648 Da / Num. of mol.: 1 Fragment: GP120 CORE, (UNP RESIDUES 43-122, 201-303, 325-486) Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Antibody , 2 types, 2 molecules HL
#3: Antibody | Mass: 26125.270 Da / Num. of mol.: 1 / Fragment: 8ANC195 HEAVY CHAIN, IG GAMMA-1 CHAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#4: Antibody | Mass: 23401.984 Da / Num. of mol.: 1 / Fragment: 8ANC195 LIGHT CHAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 6 types, 9 molecules ![](data/chem/img/NAG.gif)
#5: Polysaccharide | #6: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #7: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #8: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #9: Polysaccharide | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #12: Sugar | |
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-Non-polymers , 2 types, 3 molecules ![](data/chem/img/EPE.gif)
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#10: Chemical | ChemComp-EPE / |
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#11: Chemical |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.83 Å3/Da / Density % sol: 56.51 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion / pH: 7.3 / Details: PEG 3350, HEPES, benzamidine |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 2, 2013 | ||||||||||||||||||
Radiation | Monochromator: LIQUID NITROGEN-COOLED DOUBLE CRYSTAL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray / Wavelength: 1.033 | ||||||||||||||||||
Radiation wavelength | Wavelength: 1.033 Å / Relative weight: 1 | ||||||||||||||||||
Reflection | Resolution: 2.9→39.22 Å / Num. obs: 36730 / % possible obs: 98.9 % / Redundancy: 6.4 % / Rmerge(I) obs: 0.133 / Rpim(I) all: 0.06 / Net I/σ(I): 9.7 | ||||||||||||||||||
Reflection shell |
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-Phasing
Phasing | Method: ![]() | |||||||||
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Phasing MR |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4P9M, 3LQA Resolution: 3→39.22 Å / SU ML: 0.42 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 31.22 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 66.79 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 3→39.22 Å
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Refine LS restraints |
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LS refinement shell |
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